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NM_005219.5(DIAPH1):c.3220C>G (p.Gln1074Glu) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Sep 22, 2024
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001903786.7

Allele description [Variation Report for NM_005219.5(DIAPH1):c.3220C>G (p.Gln1074Glu)]

NM_005219.5(DIAPH1):c.3220C>G (p.Gln1074Glu)

Gene:
DIAPH1:diaphanous related formin 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
5q31.3
Genomic location:
Preferred name:
NM_005219.5(DIAPH1):c.3220C>G (p.Gln1074Glu)
HGVS:
  • NC_000005.10:g.141527626G>C
  • NG_011594.2:g.96430C>G
  • NM_001079812.3:c.3193C>G
  • NM_001314007.2:c.3220C>G
  • NM_005219.5:c.3220C>GMANE SELECT
  • NP_001073280.1:p.Gln1065Glu
  • NP_001300936.1:p.Gln1074Glu
  • NP_005210.3:p.Gln1074Glu
  • LRG_1117t1:c.3193C>G
  • LRG_1117t2:c.3220C>G
  • LRG_1117:g.96430C>G
  • LRG_1117p1:p.Gln1065Glu
  • LRG_1117p2:p.Gln1074Glu
  • NC_000005.9:g.140907193G>C
Protein change:
Q1065E
Links:
dbSNP: rs1012562287
NCBI 1000 Genomes Browser:
rs1012562287
Molecular consequence:
  • NM_001079812.3:c.3193C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001314007.2:c.3220C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_005219.5:c.3220C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Autosomal dominant nonsyndromic hearing loss 1
Synonyms:
KONIGSMARK SYNDROME; DEAFNESS, AUTOSOMAL DOMINANT 1, WITH OR WITHOUT THROMBOCYTOPENIA
Identifiers:
MONDO: MONDO:0007424; MedGen: C1852282; Orphanet: 90635; OMIM: 124900
Name:
Progressive microcephaly-seizures-cortical blindness-developmental delay syndrome
Synonyms:
Seizures, cortical blindness, and microcephaly syndrome
Identifiers:
MONDO: MONDO:0014714; MedGen: C5567650; OMIM: 616632

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002170232Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Sep 22, 2024) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9..

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002170232.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 1074 of the DIAPH1 protein (p.Gln1074Glu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DIAPH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1405413). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The glutamic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 16, 2025